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Centrosome localization determines neuronal polarity


Neuronal polarization occurs shortly after mitosis. In neurons differentiating in vitro, axon formation follows the segregation of growth-promoting activities to only one of the multiple neurites that form after mitosis1,2. It is unresolved whether such spatial restriction makes use of an intrinsic program, like during C. elegans embryo polarization3, or is extrinsic and cue-mediated, as in migratory cells4. Here we show that in hippocampal neurons in vitro, the axon consistently arises from the neurite that develops first after mitosis. Centrosomes, the Golgi apparatus and endosomes cluster together close to the area where the first neurite will form, which is in turn opposite from the plane of the last mitotic division. We show that the polarized activities of these organelles are necessary and sufficient for neuronal polarization: (1) polarized microtubule polymerization and membrane transport precedes first neurite formation, (2) neurons with more than one centrosome sprout more than one axon and (3) suppression of centrosome-mediated functions precludes polarization. We conclude that asymmetric centrosome-mediated dynamics in the early post-mitotic stage instruct neuronal polarity, implying that pre-mitotic mechanisms with a role in division orientation may in turn participate in this event.

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Figure 1: The first sprout contains polarized growth information.
Figure 2: Cytoplasmic asymmetry marks the area of neuronal polarization.
Figure 3: Centrosome/Golgi position is opposite the plane of mitotic division.
Figure 4: Centrosomal polarized activity is necessary and sufficient to induce neuronal polarity.


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We would like to thank E. Cassin and B. Hellias for the hippocampal neurons, L. Ciapponi and the Bloomington Stock Center for fly strains, and C. Gonzalez for advice with the neuroblast division experiment. F.C.dA. is supported by an EMBO long-term fellowship. J.S.D.S. was supported by an FCT/PRAXIS XXI scholarship (Portuguese Ministry of Science and Technology). F.F. was supported by an Alexander von Humboldt scholarship. Part of this work is supported by an EU Contract grant (APOPIS) to C.G.D.Author Contributions F.C.d.A. and G.P. were responsible for all in vitro experiments in mammalian and insect neurons, respectively. J.S.D.S. supervised the hippocampal neuron work. P.G.C. helped with the in situ work.

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Correspondence to Fabian Feiguin or Carlos G. Dotti.

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Supplementary information

Supplementary Figure S1

The first sprout contains neuronal polarity information. (PDF 229 kb)

Supplementary Figure S2

Organelle polarization marks the site of neuronal polarity. (PDF 496 kb)

Supplementary Figure S3

Drosophila neurons' polarization in vitro and in situ correlates with plane of mitotic division and the localization of the centrosomes. (PDF 592 kb)

Supplementary Figure S4

Centrosomal-mediated polarized microtubule and membrane activities precede morphological polarization in vitro and in situ. (PDF 177 kb)

Supplementary Figure S5

Pharmacological disruption of microtubule polymerization and membrane trafficking prevents morphological polarization. (PDF 99 kb)

Supplementary Figure Legends S1-S5 (DOC 30 kb)

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de Anda, F., Pollarolo, G., Da Silva, J. et al. Centrosome localization determines neuronal polarity. Nature 436, 704–708 (2005).

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